Ruosaari Salla T, Nymark Penny E H, Aavikko Mervi M, Kettunen Eeva, Knuutila Sakari, Hollmén Jaakko, Norppa Hannu, Anttila Sisko L
Biological Mechanisms and Prevention of Work-related Diseases, Health and Work Ability, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland.
Carcinogenesis. 2008 May;29(5):913-7. doi: 10.1093/carcin/bgn068. Epub 2008 Mar 13.
Exposure to asbestos is known to induce lung cancer, and our previous studies have suggested that specific chromosomal regions, such as 19p13, are preferentially aberrant in lung tumours of asbestos-exposed patients. Here, we further examined the association between the 19p region and exposure to asbestos using array comparative genomic hybridization and fluorescence in situ hybridization (FISH) in lung tumours and FISH characterization of asbestos-induced micronuclei (MN) in human bronchial epithelial BEAS 2B cells in vitro. We detected an increased number of 19p losses in the tumours of asbestos-exposed patients in comparison with tumours from non-exposed subjects with similar distribution of tumour histology in both groups (13/33; 39% versus 3/25; 12%, P = 0.04). In BEAS 2B cells, a 48 h exposure to crocidolite asbestos (2.0 microg/cm(2)) was found to induce centromere-negative MN-harbouring chromosomal fragments. Furthermore, an increased frequency of rare MN containing a 19p fragment was observed after the crocidolite treatment in comparison with untreated controls (6/6000 versus 1/10 000, P = 0.01). The results suggest that 19p has significance in asbestos-associated carcinogenesis and that asbestos may be capable of inducing specific chromosome aberrations.
已知接触石棉会诱发肺癌,我们之前的研究表明,特定的染色体区域,如19p13,在接触石棉患者的肺部肿瘤中优先出现异常。在此,我们使用阵列比较基因组杂交和荧光原位杂交(FISH)技术,进一步检测了19p区域与石棉暴露之间的关联,检测对象包括肺部肿瘤组织,并通过FISH技术对体外培养的人支气管上皮BEAS 2B细胞中石棉诱导的微核(MN)进行了表征。与两组肿瘤组织学分布相似的未接触石棉的受试者的肿瘤相比,我们在接触石棉患者的肿瘤中检测到19p缺失数量增加(13/33;39% 对3/25;12%,P = 0.04)。在BEAS 2B细胞中,发现暴露于青石棉(2.0微克/平方厘米)48小时可诱导含有着丝粒阴性MN的染色体片段。此外,与未处理的对照组相比,青石棉处理后观察到含有19p片段的罕见MN频率增加(6/6000对1/10000,P = 0.01)。结果表明,19p在石棉相关致癌过程中具有重要意义,并且石棉可能能够诱导特定的染色体畸变。